title: Effects of human PrPSc type and PRNP genotype in an in-vitro conversion assay.
abstract: Prion protein type and codon 129 genotype are thought to be major determinants of susceptibility and phenotype in human prion diseases. Using an in-vitro system (protein misfolding cyclic amplification) we have attempted to model human prion protein conversion using the abnormal prion protein associated with each of the major sporadic Creutzfeldt-Jakob disease subtypes, in substrates containing the normal cellular form of the prion protein of each of the three possible human PRNP codon 129 polymorphic genotypes. The prion protein type is converted with fidelity in these amplification reactions, but the efficiency of conversion depends both on the methionine/valine polymorphic status of the sporadic Creutzfeldt-Jakob disease seed and substrate homogenate, and on the abnormal prion protein type.
authors.affiliation: National CJD Surveillance Unit, School of Molecular and Clinical Medicine (Pathology), The Roslin Institute, Edinburgh, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Peden
authors.forename: Darren
authors.initials: D
authors.lastname: Wight
authors.forename: Christopher
authors.initials: C
authors.lastname: Prowse
authors.forename: Ian
authors.initials: I
authors.lastname: Macgregor
authors.forename: Jean
authors.initials: J
authors.lastname: Manson
authors.forename: Marc
authors.initials: M
authors.lastname: Turner
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
mesh_terms: D000818:Animals; D001344:Autopsy; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D005838:Genotype; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D003062:Codon; C512656:PRNP protein, human; D018620:PrPSc Proteins; D000072002:Prion Proteins; D011328:Prions